A protein molecule spontaneously adopts its native three- dimensional conformation under physiological conditions in consequence of an exquisite stereochemical code. The expression of this code that results in a transition from a denatured to the native state is called protein folding. Proteins in vivo assume the same conformations as proteins in vitro in many if not in all instances, a finding that places this problem in the realm of biophysical chemistry. our principal goal is to elucidate the stereochemical code that governs protein folding and use it to formulate a practical folding algorithm. The approach we have been pursuing is coupled to a curriculum of structural analysis showing that the problem can be naturally simplified by dividing it into smaller, quasi-independent parts. Candidates for independent treatment are called domains or compact units; these are contiguous chain regions in proteins with folded structures that are both compact and spatially distinct. Recently, we have exhaustively partitioned a data base of x-ray elucidated proteins into their composite units, using a highly sensitive measure of compactness. Now, we plan to model both the conformation of individual units and interactions between units. Of particular interest are loops, a significant category of nonrepetitive secondary structure that has been inappropriately classified as "random coil" in conformational studies. Globular proteins contain an abundant population of loops, on the order of 4 per molecule. Loops are highly compact, globular structures that are localized at the protein surface where they are poised to play important roles in the function, evolution, and immunology of the molecule. We also plan to explore a secondary structure method in which a segment of known sequence is "posed" in each of three trial states - helix, strand of sheet, and loop - and the energy of each is calculated. Finally, we wish to extend our docking algorithm to study interactions between compact units. Currently, the algorithm can identify topographic surface features, the "hills" and "valleys" of molecular dimension. Evaluation of docking between complementary features in interacting units will resort to an array processor to calculate an interunit potential of mean force in water.